Detection and quantification of regional cortical gray matter damage in multiple sclerosis utilizing gradient echo MRI

Cortical gray matter (GM) damage is now widely recognized in multiple sclerosis (MS). The standard MRI does not reliably detect cortical GM lesions, although cortical volume loss can be measured. In this study, we demonstrate that the gradient echo MRI can reliably and quantitatively assess cortical GM damage in MS patients using standard clinical scanners. High resolution multi-gradient echo MRI was used for regional mapping of tissue-specific MRI signal transverse relaxation rate values (R2(*)) in 10 each relapsing-remitting, primary-progressive and secondary-progressive MS subjects. A voxel spread function method was used to correct artifacts induced by background field gradients. R2(*) values from healthy controls (HCs) of varying ages were obtained to establish baseline data and calculate ΔR2(*) values - age-adjusted differences between MS patients and HC. Thickness of cortical regions was also measured in all subjects. In cortical regions, ΔR2(*) values of MS patients were also adjusted for changes in cortical thickness. Symbol digit modalities (SDMT) and paced auditory serial addition (PASAT) neurocognitive tests, as well as Expanded Disability Status Score, 25-foot timed walk and nine-hole peg test results were also obtained on all MS subjects. We found that ΔR2(*) values were lower in multiple cortical GM and normal appearing white matter (NAWM) regions in MS compared with HC. ΔR2(*) values of global cortical GM and several specific cortical regions showed significant (p < 0.05) correlations with SDMT and PASAT scores, and showed better correlations than volumetric measures of the same regions. Neurological tests not focused on cognition (Expanded Disability Status Score, 25-foot timed walk and nine-hole peg tests) showed no correlation with cortical GM ΔR2(*) values. The technique presented here is robust and reproducible. It requires less than 10 min and can be implemented on any MRI scanner. Our results show that quantitative tissue-specific R2(*) values can serve as biomarkers of tissue injury due to MS in the brain, including the cerebral cortex, an area that has been difficult to evaluate using standard MRI.